Dentistry

The specialty of Dental Surgery has progressed from the "blood and acrylic" of the early seventies. Dentistry has undergone a quantum leap over the past twenty-five years, with improvements in both technique and technology, bringing us the sophisticated procedures used in today's practice.peer-reviewe

Feasibility study of early outpatient review and early cardiac rehabilitation after cardiac surgery: mixed-methods research design-a study protocol.

INTRODUCTION: Following cardiac surgery, patients currently attend an outpatient review 6 weeks after hospital discharge, where recovery is assessed and suitability to commence cardiac rehabilitation (CR) is determined. CR is then started from 8 weeks. Following a median sternotomy, cardiac surgery patients are required to refrain from upper body exercises, lifting of heavy objects and other strenuous activities for 12 weeks. A delay in starting CR can prolong the recovery process, increase dependence on family/carers and can cause frustration. However, current guidelines for activity and exercise after median sternotomy have been described as restrictive, anecdotal and increasingly at odds with modern clinical guidance for CR. This study aims to examine the feasibility of bringing forward outpatient review and starting CR earlier. METHODS AND ANALYSES: This is a multicentre, randomised controlled, open feasibility trial comparing postoperative outpatient review 6 weeks after hospital discharge, followed by CR commencement from 8 weeks (control arm) versus, postoperative outpatient review 3 weeks after hospital discharge, followed by commencement of CR from 4 weeks (intervention arm). The study aims to recruit 100 eligible patients, aged 18-80 years who have undergone elective or urgent cardiac surgery involving a full median sternotomy, over a 7-month period across two centres. Feasibility will be measured by consent, recruitment, retention rates and attendance at appointments and CR sessions. Qualitative interviews with trial participants and staff will explore issues around study processes and acceptability of the intervention and the findings integrated with the feasibility trial outcomes to inform the design of a future full-scale randomised controlled trial. ETHICS AND DISSEMINATION: Ethics approval was granted by East Midlands-Derby Research Ethics Committee on 10 January 2019. The findings will be presented at relevant conferences disseminated via peer-reviewed research publications, and to relevant stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN80441309

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies

Final report on project SP1210: Lowland peatland systems in England and Wales – evaluating greenhouse gas fluxes and carbon balances

Lowland peatlands represent one of the most carbon-rich ecosystems in the UK. As a result of widespread habitat modification and drainage to support agriculture and peat extraction, they have been converted from natural carbon sinks into major carbon sources, and are now amongst the largest sources of greenhouse gas (GHG) emissions from the UK land-use sector. Despite this, they have previously received relatively little policy attention, and measures to reduce GHG emissions either through re-wetting and restoration or improved management of agricultural land remain at a relatively early stage. In part, this has stemmed from a lack of reliable measurements on the carbon and GHG balance of UK lowland peatlands. This project aimed to address this evidence gap via an unprecedented programme of consistent, multi year field measurements at a total of 15 lowland peatland sites in England and Wales, ranging from conservation managed ‘near-natural’ ecosystems to intensively managed agricultural and extraction sites. The use of standardised measurement and data analysis protocols allowed the magnitude of GHG emissions and removals by peatlands to be quantified across this heterogeneous data set, and for controlling factors to be identified. The network of seven flux towers established during the project is believed to be unique on peatlands globally, and has provided new insights into the processes the control GHG fluxes in lowland peatlands. The work undertaken is intended to support the future development and implementation of agricultural management and restoration measures aimed at reducing the contribution of these important ecosystems to UK GHG emissions

Chimpanzee gestural exhanges share temporal structure with human language

Funding: G.B., C.Ho., A.Sa., and K.E.G. were supported by funding from the European Research Council under the Gestural Origins Grant No: 802719. K.E.S. and C.W. were supported by funding from the European Research Council under Grant No. ERC_CoG2016_724608 for data collected in Kibale. K.E.G. was supported by the Russell Trust Award from the University of St Andrews for data collection in Kalinzu. S.W.T. and C.Z. were funded by the Swiss National Science Foundation (grant number: PP00P3_198912).Humans regularly engage in efficient communicative conversations, which serve to socially align individuals1 . In conversations, we take fast-paced turns using a human-universal structure of deploying and receiving signals which shows consistent timing across cultures2 . We report here that chimpanzees also engage in rapid signal-to-signal turn-taking during face-to-face gestural exchanges with a similar average latency between turns to that of human conversation. This correspondence between human and chimpanzee face-to-face communication points to shared underlying rules in communication. These structures could be derived from shared ancestral mechanisms or convergent strategies that enhance coordinated interactions or manage competition for communicative ‘space’.Peer reviewe

Characterization of the John A. Galt telescope for radio holography with CHIME

The Canadian Hydrogen Intensity Mapping Experiment (CHIME) will measure the 21 cm emission of astrophysical neutral hydrogen to probe large scale structure at redshifts z=0.8-2.5. However, detecting the 21 cm signal beneath substantially brighter foregrounds remains a key challenge. Due to the high dynamic range between 21 cm and foreground emission, an exquisite calibration of instrument systematics, notably the telescope beam, is required to successfully filter out the foregrounds. One technique being used to achieve a high fidelity measurement of the CHIME beam is radio holography, wherein signals from each of CHIME's analog inputs are correlated with the signal from a co-located reference antenna, the 26 m John A. Galt telescope, as the 26 m Galt telescope tracks a bright point source transiting over CHIME. In this work we present an analysis of several of the Galt telescope's properties. We employ driftscan measurements of several bright sources, along with background estimates derived from the 408 MHz Haslam map, to estimate the Galt system temperature. To determine the Galt telescope's beam shape, we perform and analyze a raster scan of the bright radio source Cassiopeia A. Finally, we use early holographic measurements to measure the Galt telescope's geometry with respect to CHIME for the holographic analysis of the CHIME and Galt interferometric data set

Perception Test: A Diagnostic Benchmark for Multimodal Video Models

We propose a novel multimodal video benchmark - the Perception Test - to evaluate the perception and reasoning skills of pre-trained multimodal models (e.g. Flamingo, BEiT-3, or GPT-4). Compared to existing benchmarks that focus on computational tasks (e.g. classification, detection or tracking), the Perception Test focuses on skills (Memory, Abstraction, Physics, Semantics) and types of reasoning (descriptive, explanatory, predictive, counterfactual) across video, audio, and text modalities, to provide a comprehensive and efficient evaluation tool. The benchmark probes pre-trained models for their transfer capabilities, in a zero-shot / few-shot or limited finetuning regime. For these purposes, the Perception Test introduces 11.6k real-world videos, 23s average length, designed to show perceptually interesting situations, filmed by around 100 participants worldwide. The videos are densely annotated with six types of labels (multiple-choice and grounded video question-answers, object and point tracks, temporal action and sound segments), enabling both language and non-language evaluations. The fine-tuning and validation splits of the benchmark are publicly available (CC-BY license), in addition to a challenge server with a held-out test split. Human baseline results compared to state-of-the-art video QA models show a significant gap in performance (91.4% vs 43.6%), suggesting that there is significant room for improvement in multimodal video understanding. Dataset, baselines code, and challenge server are available at https://github.com/deepmind/perception_testComment: 25 pages, 11 figure

Regional Histopathology and Prostate MRI Positivity: A Secondary Analysis of the PROMIS Trial

Background: The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. / Purpose: To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. / Materials and Methods: In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3–5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. / Results: Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9; P < .001) or Gleason score greater than or equal to 4+3 (OR, 8.7; 95% CI: 4.5, 17.0; P < .001). MCCL also determined visibility (OR, 1.24 per millimeter increase; 95% CI: 1.15, 1.33; P < .001), but odds were lower with each prostate volume doubling (OR, 0.7; 95% CI: 0.5, 0.9). In men who were TPM-negative, the presence of PIN increased the odds of zonal visibility (OR, 3.7; 95% CI: 1.5, 9.1; P = .004). / Conclusion: An incremental relationship between cancer burden and prostate MRI visibility was observed. Prostatic intraepithelial neoplasia contributed to false-positive MRI findings